White Matter Microstructure and Cognition in Non-neuropsychiatric Systemic Lupus Erythematosus

Abstract

This study examined white matter (WM) structural and metabolic alterations in relation to cognition in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). SLE can produce cognitive impairment even without overt neuropsychiatric features, but the pathogenesis of this dysfunction is not well understood. Our preliminary study of non-NPSLE found evidence correlating cognitive impairment with increased choline/creatine (Ch/Cr) in frontal lobe WM. Subjects included 60 non-NPSLE patients and 24 controls. Magnetic resonance imaging and magnetic resonance spectroscopy were performed, and a battery of neuropsychologic tests was administered. Structural and metabolic measures were analyzed and correlated with neuropsychologic data. No significant differences were found in total brain, gray matter, and WM volumes, or in frontal WM N-acetylaspartate/Cr, but the non-NPSLE group had significantly increased Ch/Cr in frontal WM. A WM cognitive score (WMCS) that included the Paced Auditory Serial Addition Task, Letter Fluency, and Animal Naming was found to correlate with total WM volume, and lower WMCS correlated with higher left frontal WM Ch/Cr. Non-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.